The present invention relates generally to novel chemical compounds and compositions, a process for preparing them, and use of these compounds and compositions as cytostatic, hypotensive and analgesic agents or for therapies involving all three properties.
Briefly, the compositions are prepared by mixing a specified part of a dialdehyde, .alpha.-keto-aldehyde or diketone with one part of an enediol or acyloin compound and allowing the mixture to react for prolonged time at room temperature. Following purification and sterilization, the composition is administered to animals harboring cancer cells. After administration, the cancer tissue is relieved of pressure by edema and further tumor development is arrested. Patients also experience a general loss of pain and a decrease in blood pressure.
For many years scientists have searched for an effective treatment for all types of cancer. Despite a great deal of interest and many important discoveries, these efforts have yet to make a major breakthrough in the cure or treatment of cancer.
According to A. Szent-Gyorgyi's bioelectronic theory of protein interactions (Szent-Gyorgy, A., Electronic Biology and Cancer, M. Dekker, New York, 1976), methylglyoxal may play an important role in controlling cell division by virtue of its properties as a powerful electron acceptor. It interacts with proteins by means of its aldehydic carbonyl by attacking the primary amino groups of proteins. Independent of whether this theory proves in fact to be true, such regulation of cell division by methylglyoxal may be useful in the development of effective chemotherapeutic agents. However, methylglyoxal and related compounds are extremely labile in vivo due to the action of a glyoxalase enzyme system which converts it to D-lactic acid in the presence of reduced gluthathione. Therefore any in vivo test of methylglyoxal for its effect on cell division would prove negative because of the action of glyoxalase.
Szent-Gyorgyi extends his bioelectronic theory to explain cancer as a disturbance of the electronic configuration of proteins in cancer cells. (Szent-Guorgyi, The Living State and Cancer, in press). Briefly stated, he speculates that methylglyoxal and related compounds re-establish the proper protein configuration and cause cancer cells to revert from the abnormal state to proliferation to the normal `resting condition`.
The use of a composition derived from methylglyoxal for the treatment of various cancers has been studied by Freireich, et al. (Cancer Chemotherapy Reports, Vol. 16, pp. 183-186, 1962). They reported clinical studies of methylglyoxal bis(guanylhydrazone) in patients with acute myelocytic leukemia and observed a complete remission frequency of 69% in 13 patients, leaving no doubt concerning its antitumor activity, particularly, they point out, when it is recalled that all then-current therapy could give only 13% complete remissions.
Additionally, in U.S. Pat. No. 2,893,912, Musser and Underwood present data to show that certain cyclic glyoxal compounds, e.g., cyclohexylglyoxal, benzylglyoxal, etc., have antiviral activity. In view of the current evidence that some forms of cancer are correlated with the occurrence of viral chromosomes in cancer cells, one may speculate that these compounds have potential in the prevention, cure and treatment of viral disease, including some forms of cancer.
U.S. Pat. No. 2,927,054 discloses the condensation of certain sugars, e.g., glucose, mannose, fructose, etc., with an aldehyde or ketone to form cyclic acetals of the sugar. The mechanism apparently involves the elimination of water by union of the oxygen of the carbonyl group of the aldehyde or ketone and the hydrogen from each of two hydroxyl groups of the sugar. This condensation reaction proceeds upon heating the mixture to the boiling point of the aldehyde in the presence of an acid acetalization catalyst, conditions favoring the open chain form of the sugar. The two adjacent carbon atoms of the cyclic acetal ring are adjacent carbons of the aliphatic chain of the sugar molecule. Several of such cyclic acetal rings may be formed on the same sugar molecule, forming poly-(cyclic acetals).